INTERVIEW: Expert Emphasises Selenium's Nutritional Role in Preventing Cancer in 'Aftermath' of Contradictory Medical Study

Consumers worldwide are regularly subjected to an overload of conflicting information and scientific claims about the benefits of nutrients, such as selenium. In recent news, a scientific trial now questions the trace mineral's role as a cancer preventive agent.

Dr. Mark E. Whitacre, Chief Operating Officer at Cypress Systems, Inc. - a Fresno, California-based biotech company - and selenium expert, argues that this latest trial did not look at the full picture.

This study - the Selenium and Vitamin E Cancer Prevention Trial (SELECT) - was conducted by the American Medical Association. It was carried out on over 35,000 men to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.

SELECT showed that, although there was pre-trial data indicating the potential of selenium and vitamin E for preventing prostate cancer, selenium alone, or in combination with vitamin E, at the doses and formulations used, did not prevent prostate cancer in the studied population ("Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers" JAMA. 2009;301(1):39-51. Published December 9, 2008).

Reacting to this finding, Dr. Whitacre argues that the study only chose to focus on selenomethionine (SeMet) and not high-selenium yeast.

Commenting on the SELECT study, Whitacre said:

"We and many other selenium experts believe that the SELECT study should have included the standardized high-selenium yeast, which was already well documented to be effective in reducing cancer risk in animal studies and human clinical trials. High-selenium yeast is different from the single synthetic amino acid compound, selenomethionine (SeMet), used in the SELECT study.  High-selenium yeast contains several different natural anabolic and catabolic forms of organically-bound selenium in addition to SeMet, such as selenocysteine, methylselenocysteine, and several other selenium compounds, all organically bound.

We suspect that the advantage of high-selenium yeast lies in its content of multiple forms of selenium, including some forms that are more effective than SeMet in anti-carcinogenesis.

The SELECT study found no cancer risk reduction activity of one chemical form of selenium, namely selenomethionine (SeMet) used at a single dose.  While the study did not add support to the earlier studies, we find that the SELECT study does not call into question earlier clinical trials that have been published in scientific journals. 

More importantly, the SELECT study does not shift the overwhelming scientific support that selenium has an important role in cancer risk reduction. A very extensive body of animal and cell culture data further provides strong evidence to support the human clinical results where high-selenium yeast has been shown to be effective in reducing the risk of certain types of cancer. In addition, the lack of effect of SeMet for cancer prevention in the SELECT study is consistent with the previous animal data".

For example, Dr. McCormick at the Experimental Toxicology and Carcinogenesis Division, IIT Research Institute in Chicago, found no effects with SeMet supplementation on the prevention of prostate cancer in rats (Eur Urol 1999;35:464-467). Furthermore, research at Purdue University found high-selenium yeast to be more effective than SeMet in the reducing DNA damage in canine prostate cells (Waters et al, J. Natl Cancer Inst (2003); 95:237-240).

Expanding on why there may be differences between SeMet and High Se Yeast, Dr. Whitacre goes on to say that the underlying mechanisms for selenium and anti-carcinogenesis were identified in a recent publication (Jackson & Combs, Current Opinion in Clinical Nutrition and Metabolic Care (2008) 11:718-726). 

This work shows that another scientific possibility that may account for the lack of effect of SeMet in SELECT study is that free-SeMet is not being used like protein-bound SeMet in high-selenium yeast.

For example, free-SeMet may be more susceptible to oxidation (which then converts to selenomethionine selenoxide) than it is within a protein, due to some sort of protection because of the tertiary-folding of the protein itself. We know that SeMet is more sensitive to oxidation than its S-analogue and as a result of its oxidation it would reduce its bioavailability.

Dr. Whitacre also highlights the fact that one of the SELECT study’s authors, Dr. Alan R. Kristal, stated in a recent editorial that the possibility remains that the decisions of SELECT on dose and formulation were wrong (Cancer Epidemiology Biomarkers & Prevention 17, 3289-3291, December 1, 2008). 

Dr. Whitacre adds that the SELECT authors, Lippman et al, quoted that “Potential limitations of SELECT include that it did not test different formulations or doses of selenium and vitamin E and that it did not definitively assess results in subgroups of men who may have responded differently than did the overall population” (JAMA, Dec. 9, 2008 online edition and JAMA, Jan. 7, 2009-Vol. 301, No. 1, print version).

Besides the original 1996 Gold-Standard clinical trial, Dr. Whitacre also highlights other studies which have been published since.

For instance, in 2002, researchers at the Penn State Hershey Cancer Institute found that supplementation with high-selenium yeast, reduced oxidative stress and serum PSA levels, risk factors for prostate cancer in humans (El-Bayoumy et al, Cancer Epidemiology Vol. 11, 1459-1465, Nov., 2002). Current research at Penn State Hershey Cancer Research Institute is aimed at comparing high-selenium yeast and SeMet on biomarkers of prostate cancer risk. This research was recently funded by the National Cancer Institute (NCI). 

More recently, in January 2009, Dr. El-Bayoumy discussed that his research, which used high-selenium yeast instead of SeMet, has shown a benefit for selenium for cancer risk reduction. Moreover, Dr. El-Bayoumy found the mechanisms of prevention to be far-reaching, “Collectively, based on mechanistic studies conducted in our laboratory and others in preclinical systems, it appears that selenium can alter cellular and molecular targets implicated in prostate cancer progression, recurrence, and metastasis, and thus selenium compounds have the potential to promote prostate cancer survivorship” (Oncology Times, Jan. 10, 2009-Vol. 31, No. 1).

In addition, there are numerous other ongoing human clinical selenium trials listed at the CLINICAL TRIALS.gov website.  Many of these trials are funded by the NCI and have the sole purpose of studying the effectiveness of selenium on cancer prevention, adds Dr. Whitacre. 

"The bottom line is that further research is currently ongoing to provide additional support that the form of selenium is of paramount importance in its effectiveness for cancer risk reduction", concludes the selenium expert.

In fact, Dr. Whitacre’s company Cypress Systems produces its own high-selenium yeast product.

Past research has shown that the company’s flagship product SelenoExcell (an organic form of selenium from yeast fermentation) supplementation can reduce the incidence of lung, colon and prostate cancers by as much as 63%, says Dr. Whitacre refering to the Gold-Standard clinical trial published in Journal of American Medical Association (JAMA) in 1996 and conducted by the University of Arizona and Cornell University (Clark, Combs, et al, JAMA, Dec. 25, 1996-vol. 276, No.24). 

"Following this publication, SelenoExcell was standardized and approved as the research standard selenium yeast source by the Division of Cancer Prevention of the National Cancer Institute (NCI), which resulted in the signing of a Clinical Trial Agreement. As a result of these efforts, SelenoExcell® has been selected as the sole intervention agent in a series of cancer prevention and health related trials that are currently being conducted by the NCI", argues Dr. Whitacre.